The proposed research aims to elucidate unresolved features in the life cycle of HBV including the regulation of expression of the various genes and the formation of the HBV viral particles, and to further investigate HBV-associated oncogenesis. The specific issues to be addressed include 1) the role and possible independent regulation of the two surface antigen promoters, an analysis of the function of the large surface antigen product, P45, characterization of the core promoter specifically in relation to the formation of the precore and core transcripts, and the possible formation of the polymerase gene. We will also investigate the interaction of the core promoter with a contiguous pol III promoter directing the formation of an RNA from the short strand. 2) Further characterization of the HBV enhancer including fine mapping and mutational analysis, determination of its activation of the various HBV promoters and elucidation of trans-acting (liver-specific) factor responsible for enhancer activity. 3) Elucidation of the function of core structures including a) the role of precore in the formation of the e antigen, including the determination of e antigen structures; b) the role of the precore in the formation of sAg/cAg compositive structures. 4) The role of integrated HBV sequences in HCC oncogenesis. These studies involve characterization of about 20 isolated hepatitis-specific and tumor-specific genes.